lupus nephritis

Post-Transplant LN Patients Can Have Viable Pregnancies

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Outcomes better in women with inactive systemic lupus erythematosus..

Having a renal transplant for lupus nephritis did not rule out successful pregnancies, but outcomes were better in those whose systemic lupus erythematosus (SLE) was inactive, according to an Italian case report.

The researchers, led by Gabriella Moroni, MD, of the Ospedale Maggiore IRCCS, in Milan, analyzed nine pregnancies in three of 38 women who had received kidney transplants at their center. Two patients had received a kidney from a living related donor and one had a received a transplant from a deceased donor.

From 2002 to 2013, five of these post-transplant pregnancies ended in miscarriage. All mothers were in their 30s by the time they conceived, and their initial pregnancies occurred at 4 years, more than 7 years, and almost 9 years after transplantation. In the last case, after two miscarriages, the woman had her first successful pregnancy more than 10 years’ post-transplant at age 38, the group wrote online in Lupus.

Miscarriages in transplanted patients are common, and preconception counseling is essential, the investigators noted.

“Women with stable and prolonged remission of SLE, normal renal function, normal blood pressure, and negative antiphospholipid antibodies (aPL) have good probabilities of positive fetal and maternal outcomes,” they explained.

However, they added that very few cases of post-transplant pregnancy in lupus nephritis (LN) patients have been reported in the literature.

In their study, patients were followed at least once a month and then followed twice weekly from 24 weeks’ gestation onward (including with serial placental Doppler imaging), hospitalized when necessary, and cared for by a multidisciplinary team of gynecologists and nephrologists.

All infants were delivered via cesarean, and the majority were of low birth rate, which may have been partly due to early surgical delivery, the authors explained. However, the infants were healthy and without serious complications, they added.

Immunosuppressive therapy consisted of steroids, calcineurin inhibitors, and mycophenolate mofetil (MMF), which had been replaced with azathioprine before conception. All patients had normal renal function and urinalysis (serum creatinine <1.5 mg/dL) and nonsignificant proteinuria (<500 mg/day). Some signs of immunological activity persisted after transplantation in two patients.

The authors stressed that before pregnancy, patients’ immunosuppressive regimens must be re-evaluated for possible teratogenic effects. They recommended switching from MMF to azathioprine. Also, ACE inhibitors must be discontinued before or at conception, they advised.

They reported that two pregnancies were uneventful. Pre-eclampsia occurred in a hypertensive patient in two pregnancies that ended in preterm delivery in one and newborns of small-for-gestational-age size in both. The authors ascribed these good results partly to the well-planned pregnancies and the specialized intensive care and imaging.

Significantly, although the risk of post-pregnancy graft loss in transplanted mothers is about around 6.9% within the first 5 years of giving birth, graft function continued to be normal in all patients. “To reduce such a risk it is wise to discourage pregnancy within the first year after transplantation,” they wrote. Urinalysis results also remained normal.

The authors noted that recent studies suggest that hydroxychloroquine improves obstetrical outcomes and should be part of immunosuppressive therapy throughout pregnancy.

“It is also important that patients start low-dose aspirin within the first trimester of pregnancy as primary prophylaxis for pre-eclampsia,” they cautioned.

Based on their experience and on published guidelines for renal transplanted patients, Moroni’s group concluded that “pregnancy in patients with kidney transplant due to LN should not be discouraged,” adding that “pre-conception counseling is mandatory.”

Treatment of severe lupus nephritis: the new horizon .

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Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.